Fully Automated Synthesis of Novel TSPO PET Imaging Ligand [18F]Fluoroethyltemazepam

Fiorenza, Dario; Nicolai, Emanuele; Cavaliere, Carlo; Fiorino, Ferdinando; Esposito, Giovanna; Salvatore, Marco

doi:10.3390/molecules26082372

Cited by 6 publications

(3 citation statements)

References 21 publications

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“…We found that that Rem not only inhibited TSPO expression (Result 5), but also reduced the expression of CRC markers, CEA and CA19-9, (Result 2). BZD is an antagonist of TSPO ( 30 ), whose application decreased TSPO expression ( 31 ), which proved that Rem reduced TSPO expression and inhibited the proliferation of HCT116, as well as the expression of CRC-markers, CEA and CA19-9, and promoted the apoptosis of HCT116. TSPO, like VDAC, is also a mitochondrial protein ( 32 , 33 ).…”

Section: Discussionmentioning

confidence: 97%

Inhibiting the Proliferation of Colorectal Cancer Cells by Reducing TSPO/VDAC Expression

Liu

Wang

Yang

2023

ijph

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Background: We aimed to explore the mechanism of the effect of remimazolam (Rem) on the proliferation of colorectal cancer (CRC) cells with CRC as a disease context. Methods: Translocation protein (TSPO) expression in CRC was determined by Western blotting and qRT-PCR in the Second Affiliated Hospital of Qiqihar Medical University from March 2019 to February 2022. TSPO-interacting proteins were predicted through string database. The proliferation was measured by CCK-8 and 5-ethynyl-2-deoxyuridine (EDU). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) and clonal colony on cells were formed to screen for the optimal concentration of Rem and to detect the viability. The expression of apoptosis-related proteins, Bcl-2 and P53, was determined by qRT-PCR and Western blotting. The effect of Rem on the expression of tumor markers, CEA and CA19-9, in CRC was examined through ELISA. Results: TSPO expression in CRC tissues and cells was higher than that in ANT samples and normal intestinal epithelial cells. Over-expression of TSPO promoted the proliferation of HCT116 and the expression of tumor markers CEA and CA19-9 and inhibited the apoptosis of HCT116. Interference with TSPO inhibited the proliferation of HCT116 and the expression of CEA and CA19-9 and promoted the apoptosis of HCT116. 1 μg/mL Rem could inhibit the viability of HCT116, the proliferation of HCT116 and the expression of CEA and CA19-9, and improve the apoptosis of HCT116. TSPO could interact with VDAC and affect its protein expression, and Rem could inhibit the proliferation and the expression of CEA and CA19-9 through the TSPO/VDAC pathway, to promote its apoptosis. Conclusion: Rem affects the proliferation of CRC cells by inhibiting the TSPO/VDAC pathway.

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Section: Discussionmentioning

confidence: 97%

Inhibiting the Proliferation of Colorectal Cancer Cells by Reducing TSPO/VDAC Expression

Liu

Wang

Yang

2023

ijph

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“…Due to its high affinities for the PBR in all species (90), it is one of the most often utilized PBR ligands, while newer, more specific ligands are beginning to take their place (91) . b) Temazepam (92) c) FGIN-143 (93) d) GML-1 (94) e) SSR-180,575 (95) . [18F] DAA1106: Automated radiosynthesis using spirocyclic iodonium ylide and preclinical evaluation for positron emission tomography imaging of translocator protein…”

Section: Agonistsmentioning

confidence: 99%

Translocator Protein TSPO (Peripheral Benzodiazepine Receptor): The Modern Story of the Ancient Preserved Protein with Ambiguous Functions

Al Mulla Hummadi

2024

IJPS

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In several tissues, including the brain, heart, blood, intestines, adrenal glands, and liver, the 18 kDa translocator protein (TSPO) was shown to be the peripheral benzodiazepine receptor. There is strong evidence that TSPO is expressed in microglial cells in the central nervous system. Five transmembrane regions are seen at the cellular level in TSPO at the contact points between the outer and inner layers of mitochondria. The cytosolic region of the complex of amino acids that binds cholesterol is where cholesterol is taken up. TSPO is found as a monomer of 18 kDa and homomultimers and homodimers. Different factors, such as cholesterol concentration and reactive oxygen species, change the multimeric structure. As a result, TSPO gains responsibility for transferring cholesterol to the mitochondrial intermembrane space, transforming it into a steroid. Additionally, TSPO appears to collaborate with other mitochondrial membrane proteins to play a part in regulating the activity of the MPTP (mitochondrial permeability transition pore) and, therefore, in the elements of apoptosis. In vivo imaging of TSPO addresses a significant test in examining brain pathology like neuroinflammatory, Alzheimer’s, and schizophrenia. Additionally, TSPO’s use as a biomarker may have important implications for developing more viable diagnostic and therapeutic approaches. The current work surveys the TSPO cellular origin and attempts to comprehend its role in various physiological and pathological conditions.

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“…137 [ 18 F]F-FETEM, [ 18 F]fluoroethyltemazepam, (3S)-7-chloro-3-[ 18 F]fluoroethyl-1-methyl-5-phenyl-3H-1,4-benzodiazepin-2one, is the newest fluorinated benzodiazepine tracer. 138 For the preparation of this radiotracer in one step, an automated synthesizer is used at a 100 °C temperature with DMSO. However, further validation for in vivo studies in neurodegenerative animal models is awaited.…”

Section: Acsmentioning

confidence: 99%

The 18-kDa Translocator Protein PET Tracers as a Diagnostic Marker for Neuroinflammation: Development and Current Standing

et al. 2022

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Translocator protein (TSPO, 18 kDa) is an evolutionary, well-preserved, and tryptophan-rich 169-amino-acid protein which localizes on the contact sites between the outer and inner mitochondrial membranes of steroid-synthesizing cells. This mitochondrial protein is implicated in an extensive range of cellular activities, including steroid synthesis, cholesterol transport, apoptosis, mitochondrial respiration, and cell proliferation. The upregulation of TSPO is well documented in diverse disease conditions including neuroinflammation, cancer, brain injury, and inflammation in peripheral organs. On the basis of these outcomes, TSPO has been assumed to be a fascinating subcellular target for early stage imaging of the diseased state and for therapeutic purposes. The main outline of this Review is to give an update on dealing with the advances made in TSPO PET tracers for neuroinflammation, synchronously emphasizing the approaches applied for the design and advancement of new tracers with reference to their structure–activity relationship (SAR).

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Fully Automated Synthesis of Novel TSPO PET Imaging Ligand [18F]Fluoroethyltemazepam

Cited by 6 publications

References 21 publications

Inhibiting the Proliferation of Colorectal Cancer Cells by Reducing TSPO/VDAC Expression

Inhibiting the Proliferation of Colorectal Cancer Cells by Reducing TSPO/VDAC Expression

Translocator Protein TSPO (Peripheral Benzodiazepine Receptor): The Modern Story of the Ancient Preserved Protein with Ambiguous Functions

The 18-kDa Translocator Protein PET Tracers as a Diagnostic Marker for Neuroinflammation: Development and Current Standing

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